Portal de Periódicos da CAPES

The H syndrome: Two novel mutations affecting the same amino acid residue of hENT3

2009; Elsevier BV; Volume: 57; Issue: 1 Linguagem: Inglês

10.1016/j.jdermsci.2009.09.011

1873-569X

Vered Molho‐Pessach, José Antonio Suárez, Christophe Perrin, C. Chiavérini, Victoria Doviner, Enriqueta Tristán‐Clavijo, Isabel Colmenero, Fabienne Giuliano, Antonio Torrelo, Abraham Zlotogorski,

Pancreatic function and diabetes

H syndrome (OMIM 612391) is a recently described autosomal-recessive genodermatosis with systemic manifestations. The disease is characterized by the major clinical findings of progressive cutaneous hyperpigmentation and hypertrichosis located mainly over the lower limbs and lower abdomen, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, low height and hyperglycemia/diabetes mellitus [ 1 Molho-Pessach V. Agha Z. Aamar S. Glaser B. Doviner V. Hiller N. et al. The H syndrome: a new genodermatosis characterized by indurated, hyperpigmented and hypertrichotic skin with systemic manifestations. J Am Acad Dermatol. 2008; 59: 79-85 Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar , 2 Molho-Pessach V. Lerer I. Abeliovich D. Agha Z. Abu Libdeh A. Broshtilova V. et al. The H syndrome is caused by mutations in the nucleoside transporter hENT3. Am J Hum Genet. 2008; 83: 529-534 Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar ]. The major histopathological findings include dermal infiltrate consisting mainly of histiocytes, later replaced by dermal and subcutaneous fibrosis [ [3] Doviner V, Maly A, Ne'eman, Z, Qawasmi R, Aamar S, Sultan M, et al. Syndrome: recently defined genodermatosis with distinct histologic features. A morphologic, histochemical, immunohistochemical and ultrastructural study of ten cases. Am J Dermatopathol; in press. Google Scholar ]. Recently, we [ [2] Molho-Pessach V. Lerer I. Abeliovich D. Agha Z. Abu Libdeh A. Broshtilova V. et al. The H syndrome is caused by mutations in the nucleoside transporter hENT3. Am J Hum Genet. 2008; 83: 529-534 Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar ] and others [ [4] Cliffe S.T. Kramer J.M. Hussain K. Robben J.H. de Jong E.K. de Brouwer A.P. et al. The SLC29A3 gene is mutated in pigmented hypertrichosis with insulin dependent diabetes mellitus syndrome and intersects with the insulin signaling pathway. Hum Mol Genet. 2009; 18: 2257-2265 Crossref PubMed Scopus (80) Google Scholar ] found that missense, nonsense, compound and deletion mutations in the SLC29A3 gene are responsible for this unique clinical picture. The SLC29A3 gene encodes the human equilibrative nucleoside transporter (hENT3), which mediates passive sodium-independent transport of nucleosides [ [5] Hyde R.J. Cass C.E. Young J.D. Baldwin S.A. The ENT family of eukaryote nucleoside and nucleobase transporters: Recent advances in the investigation of structure/function relationships and the identification of novel isoforms. Mol Membr Biol. 2001; 18: 53-63 Crossref PubMed Google Scholar ]. The exact cellular localization of hENT3, endosomal/lysosomal [ [6] Baldwin S.A. Yao S.Y. Hyde R.J. Ng A.M.L. Foppolo S. Barnes K. et al. Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes. J Biol Chem. 2005; 280: 15880-15887 Crossref PubMed Scopus (254) Google Scholar ] or mitochondrial [ [7] Govindarajan R. Leung G.P. Zhou M. Tse C.M. Wang J. Unadkat J.D. Facilitated mitochondrial import of anti-viral and anti-cancer nucleoside drugs by human equilibrative nucleoside transporter-3 (hENT3). Am J Physiol Gastrointest Liver Physiol. 2009; 296: G910-G922 Crossref PubMed Scopus (110) Google Scholar ], and its function with relation to the H syndrome is still unclear.